Unit 4 Flashcards
(140 cards)
1
Q
Importance of cell communication
A
Cell specification: Development of cells so they can do their job and cells become the right type of cell needed
Receive signals for cell division
Receive signals for cell death
Cell mating in yeast
2
Q
What types of cells communicate
A
Single and multi-celled organisms
3
Q
Quorum sensing
A
communication among bacteria to benefit population
Small signaling molecules used by bacteria to measure population
4
Q
Importance of quorum sensing
A
resistance to antibiotics
promote motility
Most often- change gene expression to benefit their life cycle
5
Q
Forms of intracellular signaling
A
Contact dependent signaling
Paracrine
Endocrine
synaptic
6
Q
Contact dependent signaling
A
signaling molecule presented as a transmembrane protein
Cells have to be in contact with each other
7
Q
Paracrine and autocrine signaling
A
binding to nearby cells; secreting molecule, released and binding to receptors on neighboring cells
autocrine: signaling molecule comes back to stimulate same cell
8
Q
Endocrine signaling
A
signaling cell releases molecule enter bloodstream and reaches target cell
Transfer over long distances
hormones
9
Q
Synaptic signaling
A
Neurotransmitter binds to target cell
Signals within neuron travels long distances because of length of axon
10
Q
Types of ligands
A
Cell surface-bound
Secreted and bind cell surface receptors
Hydrophobic small ligands diffuse across the membrane and bind to intracellular receptors (inside the cell)
11
Q
Morphogens
A
Specialized type of ligand
12
Q
What do morphogens’ effects depend on
A
Depend on how much of them are around
High levels- become cell type A
Medium levels- become cell type B
Low levels- become cell type C
13
Q
What does the reaction depend on in a cell
A
It can react in different ways depending on combination of signals that a cell receives
14
Q
How multiple signaling molecules regulate cells
A
Survive
grow and divide
differentiate
die
15
Q
Why does one signaling molecule have varied responses
A
Different receptors
Different intracellular signals with the same receptor but different intrcellular events
Different responses to different levels or amount of ligand present
16
Q
Endocrine speed, affininty, concentration of signaling
A
Takes more time with slower responses
Ligand acts at low concentrations
receptors have high affinity for ligand meaning it binds strongly
17
Q
Synaptic speed, affinity, concentration of signaling
A
Faster response
Ligand acts at high concentrations
Receptors have lower affinity for ligand
18
Q
What does the speed of signaling responses depend on
A
How far signal travels and how well receptors bind to signaling molecule
19
Q
Speed of signaling response in altering protein function
A
Fast
Ex: binding event or adding phosphate group
20
Q
Speed of signaling response in altering protein synthesis
A
Slow
Ex: making protein like Transcription, translation, folding
21
Q
Molecular switches
A
Protein kinases: add phosphate groups
Protein phosphatase: remove phosphate group
GEF: GTP binding by releasing GDP
turns things on
GAP: binds GDP by GTP hydrolysis
turns things off
22
Q
What turns proteins on and off for protein kinases and phosphatases
A
Either one
23
Q
What turns proteins on and off for GAP and GEF
A
GEF turns things on
GAP turns things off
24
Q
What are G protein-coupled receptors signaling molecules responsible for
A
Taste and smell
neurotransmitters
hormones
light
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G protein coupled receptor structure and function
7 transmembrane domains
Associate with G protein to relay signal
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Trimeric G Protein structure, function
3 subunits- a,b,y
Anchored to cytosolic leaflet of membrane
When active can bind other molecules to activate them
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Sites where amplification occurs
Something activates something else in one step
GPCR activing G protein
AC making cAMP
Enzymes
Phosphorylate kinase
glycogen phosphorylase
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Sites where amplification does not occur
Have to stay bound to something to stay active
ligand binding receptor
G protein binding cAMP
cAMP binding PKA
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4 different ways to turn signaling pathways off
Remove receptor from cell surface via endocytosis
Receptor binds to something inside cell so it can't activate next protein
Turn off proteins that function later in pathway
Activation of receptor activates molecule leading to production of inhibitory protein
30
When removing the receptor from the cell surface via endocytosis to stop the signaling pathway where can the receptor then go
The lysosome to get degraded
Held in the endosome and get recycled
31
Steps of removing GPCR from membrane via endocytosis
1.GPCR kinases phosphorylate intracellular domain of GPCR
2. GRKs acitvated by GPCR leading to its phosphorylation
3. Phosphorylation of GPCR provides binding site for arrestin
4. Arrestin bound to GPCR prevents interaction of receptor with G protein and can't activate G proteins and leads to endocytosis of receptor
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What causes the endocytosis of GPCR
Binding of arrestin to modified receptor leading to its endocytosis
33
What does arrestin do when bound to phosphorylated GPCR
prevents interaction of receptor with G proteins so it can't activate any more G proteins
leads to endocytosis of receptor
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What turns off G proteins
GAPs lead to hydrolysis of GTP to GDP and make G proteins inactive
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What happens when G proteins are inactive
they can't bind to the next molecules in the signaling pathway
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Inactivation of cAMP
cAMP binds and activates PKA
PKA activates and phosphorylates cAMP phosphodiesterase leading to inactivation of cAMP
37
What causes the inactivation of cAMP
cAMP phosphodiesterase acts on cAMP converting 5' AMP making it inactive and unable to make PKA
38
How is CREB inactivated
Dephosphorylation: protein phosphatases remove activating phosphate group turning CREB off so it can't activate transcription of more target genes
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GPCRs linked to phospholipase C Pathway
1.Ligand binds to GPCR
2. GPCR activates G protein
3. Phospholipase C cleaves phospholipid PIP2 into 2 signaling molecules DAG and IP3
4. IP3 causes Ca2+ release from ER
5. PKA activates by binding calcium and DAG
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Intracellular receptor ligands
Have to be small and hydrophobic to reach receptors inside cell
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Smooth muscle intracellular receptor
1. endothelial cell receives ACh and produces NO to diffuse into muscle cell
2. NO binds to Guanylul cyclase ad makes cGMP from GTP
3. Relaxation in smooth muscle cell
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Hormones intracellular receptors
bind to nuclear receptors, change shape, and interact with other proteins to activate transcription
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Tyrosine kinase activity
ability to add phosphate to tyrosine amino acids in protein
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Insulin signaling pathway
1. Insulin binds to insulin receptor which dimerizes and undergo cross phosphorylation
2. IRS1 phosphorluates and provides docking sites
3. PI3K adds phosphate to PIP2 to make PIP3
4. PIP3 binds to PDK1 activating PDK1
5. PDK1 phosphorylates and activates PKB causing movement of glucose into membrane
6. PKB adds Phosphate to GSK3 turning it off
7. Glycogen synthase stores glucose as glycogen
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RTK signaling via Ras
1. Growth factor binds to RTK
2. Ras binds and activates MAPKKK
3. MAPKKK activates MAPKK
4. MAPKK activates MAPK
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What is FRET used for
Test if G protein and pathway is active
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MAPK signaling: scaffolds
Scaffold help bring kinases together and speed up signaling
Prevent cross talk between molecules increasing precision of signaling events
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PI-3K-Akt signaling pathway
1. Insulin like growth faactor binds to RTK
2. RTK binds and activates PI3K
3. PI3K adds phosphate to PIP2 to make PIP3
4. AKT bound to PIP3
5. mTOR phosphorylates AKT
6. Phosphorylates Bad to inactivate and inhibit apoptosis
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Rapamycin
drug that can turn pathway off so cells die-- cancer cells
50
Tyrosine kinase associated receptors: Cytokine pathway
1. Cytokine binds to cytokine receptor and causes the dimerization of receptors
2. receptors associated with JAK
3. JAK phosphorylates itself and the receptor providing a binding site for STAT
4. STAT gets phosphorylated by JAK and dimerizes with itself and binds to DNA for regulation of transcription
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lateral inhibition
one cell inhibiting its neighbors from becoming like itself
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What proteins from signaling pathways are gene regulatory proteins
B- catenin
STAT
Notch
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What proteins are ligands from signaling pathways
Delta
Wnt
54
What proteins are effector enzymes from signaling pathways
Phospholipase C
JAK
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What protein is a second messenger from signaling pathways
PIP3
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How does FRET work
Light excites fluorescent probe proteins to test if molecule is interacting with another molecule
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If the pathway is active what will FRET show
When light shined on cell, light will be emitted but immediately absorbed
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How would you know that mutant (inactive) molecule is before the active one
If mutant shows signaling event, it is before the others
Ras is independent of molecule so if there was a signaling event still then the molecule is before ras
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How would you know that mutant molecule is after the others
If mutant does not show signaling event,/response, it will be after the others
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Mitogens
signaling molecules activating pathways that stimulate cell division
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Growth and survival factors
Growth factors: stimulate cell growth
Survival factors: signaling molecules that promote cell survival by inhibiting apoptosis
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Cell cycle phases
G1: growth phase
S Phase: DNA replication
G2: growth phase
M phase:
- Mitosis: division of cells
- Cytokinesis: division of cytoplasms
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G1 phase function
Monitor cell conditions to see if cell division is appopriate
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What is used to see what genes are important for the cell cycle
Fission yeast
Budding yeast
They both have temperature sensitive mutatins
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How can you see what proteins/transitions points are needed in the cell cycle
At high temperatures, protein can't do its job
Depending on what stage of the cell cycle the yeast is in tells what protein is needed to move into the next stage
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3 checkpoints in cell cycle
Start checkpoint: between G1 and S phase
Second checkpoint: between G2 and M phase
Monitor
Third checkpoint: between Metaphase and anaphase stage
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Start checkpoint
between G1 and S phase
Monitor environmental conditions to see if they are favorable to support more cells
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2nd checkpoint
between G2 and M phase
Monitor
- if environment is still favorable
- Ensure DNA was replicated properly in S phase so daughter cells get correct genetic information
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Third checkpoint
between Metaphase and anaphase stage
-ensure chromosomes attached to spindle correctly
-Ensures cell have the correct number of
chromosomes
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Mechanisms to ensure checkpoints are passed
Transcription regulation
Formation of cyclin Cdk complexes
Phosphorylation and dephosphorylation
Protein binding
Proteolysis/degradation
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Cyclin-dependent kinases (Cdks)
Depend on binding of cyclins to be active
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Cdk activities and amount changes
Activities rise and fall throughout cell but amount of Cdks stay the same
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Cyclins
Regulate activity of Cdks
Direct Cdks to molecules that need to get modified
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Cyclins activity and amount changes
protein levels of cyclins rise and fall throughout the cycle due to transcription and degradation and activity changes
75
How to fully activate Cdk
Produce Cyclin
Cdk Activating Kinase to phosphorylate cdk so it can start phosphorylating its target protein
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Regulation of Cyclin Cdk to turn it off
Wee 1 Kinase adds inhibitory phosphate group on Cdk to inactivate it until conditions in cell are good
77
Regulation of Cyclin Cdk to activate it again
Cdc25 phosphatase removes inhibitory phosphate groups to back to the active Cdk
78
What quickly turns cCdk complex off when there is a mutation
P27 is a Cdk inhibitor protein (CKI) produced to turn off cCDK complex by binding to it
79
How to get rid of P27 when not needed
SCF complex promotes addition of ubiquitin to CKI (P27) and can go to proteosome to get degraded
80
How mitogens start the cell cycle/division
Mitogen activates MAP kinase pathway
MAP kinase phosphorylates and activates gene regulatory proteins to activate early gene expression
81
Myk
Binds to DNA and leads to transcription of G1 cyclins
82
How to get active G1-Cdk
Myk activates transcription of G1 cyclins
G1 cyclins bind to Cdk
cdk kinase adds phosphate group activating G1-cdk`
83
What happens for G1/S and S cyclins to be made to move into S phase
G1-CDK phosphorylates and inactivates Rb (retinoblastoma) turning it off
When Rb is inactive, it turns off and can not bind to E25 so E25 can become active and helps produce G1/S and S cyclins
84
Feedback loops of first checkpoint to ensure the cell can move into the S phase
E25 production can lead to more E25
G1/S and S Cdk keep Rb off and inactivated
85
S-Cdk
Helps in DNA synthesis by phosphorylating origin recognition complex (ORC) to activate it
86
Cohesins
proteins holding sister chromatids together
start organizing for mitosis
87
When and how are centrosomes duplicated
During S phase
Triggered by G1/S-CDK complex
Start organizing for mitosis
88
Initiation of mitosis
Cdc25 phosphotase is activated to remove inhbitory phosphate group
89
Feedback loops in initiation of mitosis
Keep CDC 25 on
Keep Wee1 off
90
M phase steps
Prophase: sister chromatids condense and mitotic spindle starts to form outside nucleus
Prometaphase: break down of nuclear envelope
metaphase: chromosomes attach to spindle line up at middle of cell
Anaphase: sister chromatids separate and pulled toward spindle poles due to Kinetocore MT shortening
Telophase: Chromosomes arrive at poles and nuclear envelope reassembles
Cytokinesis: Actin and myosin separate 2 cells by using Rho
91
2 parts of anaphase
A. Shortening of kinetochore MT moves chromosomes toward centrosomes
B. Interpolar MT slides using kinesins pushing poles apart from each other and Astro MT pull poles apart
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What is used to move through third checkpoint
APC/C active when bound to Cdc2
93
APC/C
Adds ubiquitin chain so they get degraded
degrades
- M cyclins and S cyclins
- Securin
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Securin
when degraded it causes separase to be activated and to separate sister chromatids to move into anaphase
95
How our cells arrest the cell cycle in response to a damage event
Damage triggers series of events leading to phosphorylation/activation of p53 causing the production of p21/27 (cdk inhibitory protein) causing cell cycle arrest
96
How our cells arrest the cell cycle in response to excessive Myc
Excessive Myc activates Arf (inhibitor protein) binding onto Mdm2 activating p53 causing cell cycle arrest or apoptosis
97
Steps in Checkpoint 1 (G1 to S)
1. Mitogens are released and bind receptors, stimulating cell division
2.Myc protein is produced increasing production of G1 cyclins
3. G1 cyclins associate with Cdk
4. Cdk phosphorylates and inactivates the Rb protein resulting in activation of E2F
5.E2F promotes transcription of G1/S and S cyclins
6. S-Cdk promotes assembly of pre initiation complexes for DNA replication
98
Steps in Checkpoint 2 (G2 to M)
1. M cyclins bind to Cdk
2. CAK adds activating phosphate group and Wee1 adds inhibitory phosphate so mitosis can proceed
3. Cdc25 removes inhibitory phosphate group so mitosis can proceed
4. Positive feedback loops act to inhibit Wee1 and activate Cdc25
5. M-Cdk also acts to phosphorylate and activate APC/C leading to its own destruction
99
Steps in Checkpoint 3 (Metaphase to Anaphase)
1. Cdc20 binds and activates the APC
2. APC promotes activation of separase by causing degradation of securin
3. This causes break up of the cohesin complex and separation of sister chromatids during anaphase
100
Differences between Mitosis and Meiosis
Meiosis:
- germ cells
- Half the number of chromosomes as starting cell
Meiosis 1: Homologous pairs of chromosomes line up on spindle and separated in first division
Meiosis 2: sister chromatids line up and separate in 2nd division
Mitosis:
- somatic cells
- Same of chromosomes as starting cell
- Sister chromatids line up on the spindle individually
101
3 types of microtubules
Kinetochore microtubules: attach to the kinetochores bound to each sister chromatid, and
shorten during anaphase A.
Astral microtubules:positions the mitotic spindle and involved in pulling the two poles apart
in Anaphase B.
Interpolar microtubules: connect the two poles to each other. The motor protein kinesin
moves along interpolar microtubules to move the two poles apart in Anaphase B.
102
Causes for cell death
Organs/tissues have correct structure
dispose of older cells
damaging event
correct number of nerve cells
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Caspase
Enzymes that break down cell components as part of apoptosis
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the extrinsic pathway of apoptosis (steps)
1. If Killer lymphocytes encounters foreign cell, they express Fas ligand signaling molecule
2.Fas ligand binds to Fas death receptor allowing receptor to interact with FADD adaptor protein
3. FADD Allows caspase enzymes to be brought in to assemble DISC (death inducing signaling co mplex)
complex in cell
4. DISC brings multiple caspase molecules together so they can cleave each other to activate caspase
5. Initiator caspase: first class to become active and activates executioner caspases
6.Executioner caspase: cleave other molecules (proteins, DNA) in cells leading to apoptosis
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FADD
In extrinsic apoptosis pathway, Allows caspase enzymes to be brought together to assemble DISC (death inducing signaling co mplex) complex in cell
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Initiator v executioner caspase
Initiator caspase: first class to become active and activates executioner caspases
Executioner caspase: cleave other molecules (proteins, DNA) in cells leading to apoptosis
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apoptosome
multiple Apaf1s formed by binding of cytochrome C to Apaf1
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Anti-apoptotic Bcl2 proteins
Inhibit apoptosis by keeping Bax and Bak apart
maintain membrane integrity: Cytochrome C stays inside mitochondria
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BH3
When cell encounters bad event, BH3 proteins are activated and turn off anti apoptotic Bcl2 protein
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Intrinsic pathway of apoptosis (Steps)
1. When cell encounters bad event, BH3 only proteins are activated and turn off anti apoptotic Bcl2 protein
2. Inhibiting anti apoptotic Bcl2 protein prevents it from keeping Bax and Bak apart so Bax and Bak associate with each other forming channels
3. Channels allow cytochrome C to be released from mitochondria
4. Allows it to bind to Apaf1 changing Apaf1’s structure so multiple Apaf1 can form apoptosome
5. Apoptosomes can bring initiator caspases together so they can active executioner caspase
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What gets released when Bax and Bak come together
Cytochrome C
Anti-IAPs
112
IAPs
inhibit apoptosis In healthy cells, when they encounter caspase, bind and block it to protect cells
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Anti-IAPs
prevent IAPs from binding caspases
Ensures apoptosis proceeds
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How a cell could be allowed to survive
Inactivation of pro apoptotic BH3 -only Bcl2
Increased production of anti apoptotic bcl2 proteins
Inactivation of anti IAPs
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What characteristic is unqiue to cancer cells
prefer only going through glycolysis to use glucose as energy source
Have to take up much more glucose
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What detects cancerous cells
PET scans can detect increased levels of glucose uptake and metabolism
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Benign v Malignant v Metastiasized tumor
Benign tumor: non-invasive; haven't invaded underlying tissue
Malignant tumor: invasive; invade neighboring tissue pass underlying tissue
Metastasized tumor: cancer cells go farther away and form tumors in new location
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Why can mutations be present
Inheritance
Radiation
Chemical carcinogen
Errors in DNA replication
Defects in DNA repair
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What processes do mutations alter
Cell proliferation
Dna damage response
Cell growth
Alterations in cell survival
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Angiogensis
the process of making new blood vessels to spread cancer cells quicker
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Cancer cell properties
Angiogenesis
Stabilize telomere length
Increased ability to grow/proliferate
Decreased sensitivity to anti-proliferative signals
Less likely to undergo apoptosis
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Cell senescence and how cancer prevents this
Cell senescence: Natural process of a cell no longer dividing
Cancer gets around this:
Keep telomerase active so they don't shorten
Disable checkpoint so cell cycle proceeds
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What is cancer accumluated from
single cell accumulating at least 3 mutations
124
2 classes of mutations causing gene to become dangerous to cell
Overactivity mutation
Underactivity mutation
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Oncogene with examples
genes that experience overactive mutation can become dangerous and can cause cell to become cancer cell
Examples: Myk and cyclin-cdk
126
Mutations that oncogene experiences
Deletion or point mutation in coding sequence
Regulatory mutation
Gene amplification
Chromosome rearrangement
-Produce more of protein
-produce more active version of protein
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oncogene v Tumor suppressor
oncogenes cause gain of function effects
Tumor suppressor gene cause loss of function effects
128
How many genes need to be mutated in tumor suppressor gene
Both copies of the gene have to be mutated
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Mechanisms of gene inactivation (2)
Change in nucleotide sequence so protein is no longer functioning
Epigenetic changes affect ability of gene to be transcribed
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2 types of Gene inactivation by epigenetic changes
packaging of DNA as heterochromatin making it not accessible for transcription
DNA methylation of C nucleotide to turn gene off
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P53
Important Tumor suppressor genes
Keep things inactive
Components of p53 pathway mutated in all cancer
`
132
Steps to metastasis
Tumor has to be able to travel through blood stream , survive and proliferate in new tissue and form tumor
133
How virus can make it more likely to develop cancer
Viral genetic info gets integrtated into host genome making it more likely for cell to become cancerous
E6 and E7 interfere with rb and p53 tumor suppressor proteins
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Overactivity Mutation
proteins when active move through the cell cycle
Problem if the mutation is in one copy of oncogene
135
Underactivity Mutation
turns off the cell cycle
Problem if mutation in both copy of tumor suppressor genes
136
What proteins type does KIF18B gene encode
Kinesin family
137
Effect of KIF18B knock down
Decreased colony number
Decreased cell migration
Decreased invasion
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Overexpression of KIF18B
Increase cell imgration, colony number, invasion
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Knock down of KIF18B on tumor groqth
Formation of smaller tumors
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KIF18B oncogene or tumor supressor gene
oncogene promote tumor growth
